Cyclohexanones moderately hindered

The other group of moderately hindered cyclohexanones which has been examined in detailed is a group of substituted 1-decalones, which gave results similar to those of the 12-keto steroids on Li-NHs reduction. These decalones were all derived from protected diketone (51) and included two different 2-monosubstituted derivatives (52) and (53). These decalones were reduced both in the presence of a proton donor (NH4CI) and under anhydrous conditions in yields of 69-99%. The axial alcohol was the major product in the presence of a proton donor, while the equatorial alcohol was predominant in its ab-... 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

In 2009, Fu et al. developed highly 4-phenoxy-substituted prolinamide phenols, which could promote the asymmetric aldolisation of cyclohexanone with a range of aldehydes with a high degree of diastereo- and enantioselectivity in a large amount of water (Scheme 2.12). The best enantioselectivities of up to 97% ee were obtained with the most steric hindered catalyst that bore a tert-butyl group on the phenol moiety. The scope of the reaction could be extended to aliphatic ketones with enantioselectivities of up to 94% ee, albeit with low to moderate diastereoselectivities of up to 50% de. 

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